Sotalol produces torsades de pointes in a dose-dependent manner. Which property of this molecule explains both its class III action and its principal dose-limiting toxicity?
- A It is a pure IKr blocker with no other cardiac actions
- B It is a racemic mixture where the d-isomer blocks IKr while both isomers block beta receptors ✓
- C It blocks both IKr and IKs channels equally
- D It enhances IKs current while blocking beta-1 receptors selectively
Correct answer: B. It is a racemic mixture where the d-isomer blocks IKr while both isomers block beta receptors
Explanation
Sotalol is administered as a racemate. Both d- and l-isomers have non-selective beta-blocking activity, but only the d-isomer prolongs repolarization by blocking the rapid delayed rectifier potassium current (IKr). This dual property makes it unique among class III drugs. Because IKr block drives QT prolongation, torsades risk rises steeply with dose and with renal impairment since sotalol is renally cleared. It does not block IKs, and it is not a pure potassium blocker given the beta blockade.
Reference: Katzung Basic and Clinical Pharmacology, 16th ed.
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